Aminomethylpyrimidines as novel DPP-IV inhibitors: a 10(5)-fold activity increase by optimization of aromatic substituents

Bioorg Med Chem Lett. 2004 Mar 22;14(6):1491-3. doi: 10.1016/j.bmcl.2004.01.019.


The influence of aromatic substitution on a newly discovered class of inhibitors of dipeptidyl peptidase IV was investigated. A 10(5)-fold increase in potency was achieved by the optimization of aromatic substituents in a parallel chemistry program. The observed SAR could be explained by an X-ray structure of the protein-ligand complex.

MeSH terms

  • Adenosine Deaminase / metabolism
  • Adenosine Deaminase Inhibitors*
  • Glycoproteins / antagonists & inhibitors*
  • Glycoproteins / metabolism
  • Protease Inhibitors / chemistry*
  • Protease Inhibitors / metabolism
  • Pyrimidines / chemistry*
  • Pyrimidines / metabolism


  • Adenosine Deaminase Inhibitors
  • Glycoproteins
  • Protease Inhibitors
  • Pyrimidines
  • Adenosine Deaminase